Lung cancer is one of the major life-threatening cancers, with a higher mortality rate and morbidity. Curcumin acts as a potential anticancer agent but it shows less aqueous solubility so its clinical application is limited. In this present study, we developed curcumin-surface decorated Zinc Oxide nanoparticles ZnO@Cur to enhance its aqueous formulation and improve the anti-cancer activity of curcumin. The synthesized ZnO@Cur confirmed by various spectroscopies (UV-vis and fluorescence) and electroscopic techniques (Powder XRD, SEM, TEM, and DLS). ZnO@Cur dramatically suppressed the proliferation of A549 and HEL-299 cells and showed low toxicity in MTT assays. Compared with free ZnO and curcumin, ZnO@Cur significantly inhibited the migration ability of A549 cells. Moreover, the induction of apoptosis in A549 cells by ZnO@Cur was resulted by AO-EB staining. ZnO@Cur activated to promote intracellular ROS overproduction and induced apoptosis. ZnO@Cur shows excellent biocompatibility compared to free ZnO and Curcumin, the present study explained that ZnO@Cur as a safe and hopeful strategy for chemotherapeutics of lung cancer therapy and deserve for further clinical evaluations.